新型褪黑素受体激动剂Neu-P11改善胰岛素敏感性的研究

项目名称： 新型褪黑素受体激动剂Neu-P11改善胰岛素敏感性的研究

项目编号： No.81200590

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 佘美华

作者单位： 南华大学

项目金额： 23万元

中文摘要： 新型的褪黑素受体激动剂Neu-P11具有改善睡眠的作用。研究表明睡眠障碍与胰岛素抵抗（IR）的发生联系密切；我们前期研究证实Neu-P11能抑制体重增长、降低血浆糖脂水平，提示Neu-P11可能通过改善胰岛素敏感性发挥作用。本项目拟①采用胰岛素钳夹和葡萄糖转运实验，观察Neu-P11对IR的3T3-L1脂肪细胞和大鼠模型胰岛素敏感性的影响；②采用免疫组化法观察胰岛的形态结构、放免法分析离体胰岛第一相胰岛素分泌、Western blot分析IRS-1/PI3-K/Akt通路及IRS-1(Ser307)、GSK-3(Ser21)、GLUT4的表达以及采用激光共聚焦分析GLUT4的易位，阐明Neu-P11调节胰岛素敏感性的机制及胰岛素信号通路与褪黑素受体后途经的交叉点。研究将明确Neu-P11对胰岛素信号传导的影响；揭示褪黑素和胰岛素/胰岛β细胞的关系，为探索IR、2型糖尿病的治疗提供新的靶点。

中文关键词： Neu-P11；褪黑素；胰岛素抵抗；葡萄糖摄取；胰岛素敏感性

英文摘要： Neu-P11, a novel melatonin receptor agonist, has been confirmed its effect on sleep promotion. Research findings show that there is a close relationship between insulin resistance(IR), Type 2 Diabetes Mellitus(T2DM) and sleep disorders.In addition, our previous results showed that Neu-P11 inhibits increasing of body weight and decreases the level of plasm glucose,which proved the regulation effect of Neu-P11 on energy metabolism. Therefore, we hypothesize that Neu-P11 may influence the insulin sensitivity. The study will be carried out in the following two aspects: ① On the basis of the successfully-built IR models in animals and adipocytes, effect of Neu-P11 on the insulin sensitivity will be researched both in vivo and vitro in order to confirm the hypotheses of this project, and hyperinsulinemic euglycemic clamp and isotope-labeled glucose transport method will be applied; ②At the same time,the research content includes analyzing the morphous and primary phase insulin secretion of islets isolated from the animal subjects; the expression of IRS-1(Ser307),GSK-3(Ser21) as well as molecules in the insulin IRS-1/PI3-K/Akt signal pathway; expression and membrane translocation of GLUT4 in IR-adipocytes. The results will illuminate the potential mechanism by which Neu-P11 improves the insulin sensitivity, and the lin

英文关键词： Neu-P11；melatonin receptor agonist；insulin resistance；glucose uptake；insulin sensitivity